tbuckley/cabot-search huggingface dataset:
3-Hydroxy-3-Methylglutaryl—Coenzyme A Reductase Inhibitors in the Treatment of Hypercholesterolemia
Authors: Jeffrey M. Hoeg
Journal: JAMA (1987)

A new class of drugs, which inhibit de novo cholesterol biosynthesis, significantly reduces the blood cholesterol concentrations in hypercholesterolemic patients. Four separate inhibitors have lowered plasma total cholesterol and low-density lipoprotein (LDL) levels in humans by 20% to 40%: mevastatin (Compactin), lovastatin (mevinolin), pravastatin (CS-514, Eptastatin, and SQ 31 000), and simvastatin (Synvinolin, MK-733). In addition to lowering total and LDL cholesterol concentrations, the plasma concentration of the potentially atherogenic B apolipoprotein is also reduced by 20% to 40%. The reduction in the levels of circulating atherogenic lipoprotein particles occurs as a result of decreased synthesis and enhanced removal of LDLs by the LDL receptor pathway in hepatocytes. Moreover, the levels of high-density lipoprotein cholesterol, which are inversely related to atherosclerosis, increase in concentration with treatment by these drugs. If the short-term safety of these drugs extends to ongoing long-term studies and if cardiovascular morbidity and mortality are affected by their use, this class of hypolipidemic agent will markedly facilitate the effective treatment of hypercholesterolemia. (<i>JAMA</i>1987;258:3532-3536)
THE RACES THAT CONSTITUTE THE GROUP OF COMMON FIBROBLASTS
Authors: Raymond C. Parker
Journal: The Journal of Experimental Medicine (1932)

1. The ability of fibroblasts to mature and to manifest their various potencies in any particular medium is inversely proportional to the growth energy which they exhibit in that medium. Fibroblasts having access to high concentrations of food substances in their environment do not mature, regardless of their origin or the age of the animal from which they were derived. They behave as embryonic cells. 2. Fibroblasts cultivated in vitro are potentially able to produce cells with the structural and functional properties commonly attributed to macrophages. This is true regardless of their origin or the length of time which has elapsed since their isolation from the origin. 3. The fibroblast and the macrophage are considered to represent extreme functional and structural variations of the same cell type. 4. The structural and functional characteristics displayed by fibroblasts in vitro vary according to their origin and to the changes which take place in the composition of the medium in function of time.
Influenza in 1918: Recollections of the Epidemic in Philadelphia
Authors: Isaac Starr
Journal: Annals of Internal Medicine (2006)

When the great influenza epidemic struck Philadelphia in 1918, the author was just starting his third year at the University of Pennsylvania School of Medicine. After a single lecture on influenza, classes for the third and fourth year students were suspended while he and his mates manned an emergency hospital, in which they worked under little or no medical supervision and in the presence of an alarming patient mortality. This essay describes what happened in the hospital, and in the city as a whole, during the pandemic. Certain features of the clinical course of most patients permit the hope that modern therapy will prevent a repetition of the horrendous mortality.
Cutaneous Rhizopus Infection
Authors: Jay H. Mead
Journal: JAMA (1979)

A 29-year-old woman in good health except for scoliosis suffered severe sequelae during the postoperative course for placement of a Harrington rod. A cutaneous<i>Rhizopus</i>infection in and about the incision site was attributed to the use of a contaminated elasticized adhesive (Elastoplast) dressing. The contamination was established as a nosocomial problem, which is extremely difficult to control. The extent of the infection, subsequent long recovery course, and remarkable sequelae make this case unusual. (<i>JAMA</i>242:272-274, 1979)
Elucidating variations in the nucleotide sequence of Ebola virus associated with increasing pathogenicity
Authors: Stuart D Dowall, David A Matthews, Isabel García-Dorival, Irene Taylor, John Kenny, Christiane Hertz-Fowler, Neil Hall, Kara Corbin-Lickfett, Cyril Empig, Kyle Schlunegger, John N Barr, Miles W Carroll, Roger Hewson, Julian A Hiscox
Journal: Genome biology (2014)

Ebolaviruses cause a severe and often fatal haemorrhagic fever in humans, with some species such as Ebola virus having case fatality rates approaching 90%. Currently, the worst Ebola virus outbreak since the disease was discovered is occurring in West Africa. Although thought to be a zoonotic infection, a concern is that with increasing numbers of humans being infected, Ebola virus variants could be selected which are better adapted for human-to-human transmission. To investigate whether genetic changes in Ebola virus become established in response to adaptation in a different host, a guinea pig model of infection was used. In this experimental system, guinea pigs were infected with Ebola virus (EBOV), which initially did not cause disease. To simulate transmission to uninfected individuals, the virus was serially passaged five times in naïve animals. As the virus was passaged, virulence increased and clinical effects were observed in the guinea pig. An RNAseq and consensus mapping approach was then used to evaluate potential nucleotide changes in the Ebola virus genome at each passage. Upon passage in the guinea pig model, EBOV become more virulent, RNA editing and also coding changes in key proteins become established. The data suggest that the initial evolutionary trajectory of EBOV in a new host can lead to a gain in virulence. Given the circumstances of the sustained transmission of EBOV in the current outbreak in West Africa, increases in virulence may be associated with prolonged and uncontrolled epidemics of EBOV.
Epstein-Barr Virus and the Immune System
Authors: Jeffrey I. Cohen
Journal: JAMA (1997)

<h3>CASE PRESENTATION</h3> A 35-YEAR-OLD an was admitted to the Warren Grant Magnuson Clinical Center at the National Institutes of Health, Bethesda, MD, with Burkittlymphoma. The patient had been in good health until 2 months before admission, when he developed back pain. One month before admission, he noted left supraclavicular adenopathy followed by numbness in the left flank, clonus of the left leg, and a rapidly increasing mass in the left paraspinal area. He was admitted to a local hospital, where a biopsy specimen of the supraclavicular node showed lymphoma. A computed tomographic scan showed periaortic and retroperitoneal lymphadenopathy, and a magnetic resonance image showed extradural compression of the spinal cord. The patient received oral dexamethasone and radiotherapy to the area of cord compression; the back pain resolved and the paraspinal mass diminished in size. On examination at the Clinical Center, there was no apparent lymphadenopathy or hepatosplenomegaly, and
Blastoid Variants of Mantle Cell Lymphoma: Frequent bcl-1 Rearrangements at the Major Translocation Cluster Region and Tetraploid Chromosome Clones
Authors: German Ott, Jörg Kalla, M. Michaela Ott, Birgit Schryen, Tiemo Katzenberger, Justus G. Müller, Hans K. Müller-Hermelink
Journal: Blood (1997)
Reactions to Fluorescein
Authors: John E. Heffner
Journal: JAMA (1980)

<h3>To the Editor.—</h3> In a recent case report Cunningham and Balu (242: 2431, 1979) suggest that the collapse of their patient after fluorescein angiography was due to direct or indirect effects of fluorescein dye on the heart. A similar case of ours, however, suggests that fluorescein may initiate an anaphylactoid reaction producing hypotension and death on a noncardiac basis. <h3>Report of a Case.—</h3> A 78-year-old woman, without prior cardiac disease, underwent fluorescein infusion with 5 mL of 10% dye. Aften ten minutes she collapsed, and cardiopulmonary resuscitation (CPR) was initiated. After approximately five chest compressions the emergency room team arrived and noted weak pulses; CPR was discontinued. An initial blood pressure was 90/60 mm Hg, with a pulse rate of 120 beats per minute. The examination was notable for pulmonary rales and wheezes. An ECG showed sinus tachycardia without any evidence of myocardial ischemia. A chest roentgenogram showed pulmonary edema.
Treatment of Migraine Attacks with Sumatriptan
Journal: New England Journal of Medicine (1991)

The headache in migraine attacks may be caused by dilatation of certain cranial arteries or arteriovenous anastomoses, by neurogenic dural plasma extravasation, or by both of these mechanisms. Sumatriptan, a novel selective agonist of 5-hydroxytryptamine-like receptors, blocks these phenomena. We investigated its efficacy in migraine.We studied 639 patients with migraine attacks in a randomized, double-blind, placebo-controlled, parallel-group clinical trial. We assessed the effect of subcutaneous injections of 6 or 8 mg of sumatriptan or placebo on the severity of headache and associated migrane symptoms 30, 60, and 120 minutes after treatment. Patients who were not free of pain after 60 minutes subsequently received placebo if they had initially received placebo or 8 mg of sumatriptan, and 6 mg of sumatriptan or placebo if they had initially received 6 mg of sumatriptan.After 60 minutes, the severity of headache was decreased in 72 percent (95 percent confidence interval, 68 to 76 percent) of the 422 patients given 6 mg of sumatriptan, 79 percent (95 percent confidence interval, 71 to 87 percent) of the 109 patients given 8 mg of sumatriptan, and 25 percent (95 percent confidence interval, 17 to 33 percent) of the 105 patients given placebo (data on 3 patients could not be evaluated). As compared with the placebo group, 47 percent (95 percent confidence interval, 38 to 57 percent) more patients who had received 6 mg of sumatriptan and 54 percent (95 percent confidence interval, 43 to 65 percent) more patients who had received 8 mg of sumatriptan had a decrease in the severity of headache (P less than 0.001 for both comparisons). After 120 minutes, 86 to 92 percent of the 511 patients treated with sumatriptan (202 assigned to 6 mg plus placebo, 203 to 6 mg plus 6 mg, and 106 to 8 mg plus placebo) had improvement in the severity of headache, as compared with only 37 percent of the 104 patients who received placebo once or twice (P less than 0.001 for all comparisons). Twenty-one patients were excluded from the analysis because of missing data (19) or protocol violations (2). The response rates did not differ significantly among the sumatriptan regimens. Adverse events were minor and transient in all groups.We conclude that a single 6-mg dose of sumatriptan given subcutaneously is a highly effective, rapid-acting, and well-tolerated treatment for migrane attacks. The administration of a second dose 60 minutes later to patients not responding well to an initial dose affords little additional benefit.
Alteration in growth regulation of hepatocytes in primary culture obtained from cirrhotic rat: Poor response to transforming growth factor-β1 and interferons
Authors: Shinichi Kiso, Sumio Kawata, Shinji Tamura, Nobuyuki Ito, Kenji Takaishi, Yasuhiro Shirai, Hirofumi Tsushima, Yuji Matsuzawa
Journal: Hepatology (1994)

Cell growth appears to be controlled by positive and negative cell growth regulation. Little is known about the growth regulation of hepatocytes in the cirrhotic liver. Clarifying the responses of hepatocytes obtained from cirrhotic liver to various growth factors and growth inhibitory factors might aid understanding of alterations in growth regulation of the hepatocytes in the cirrhotic liver. We investigated the effects of hepatocyte growth factor, epidermal growth factor, heparin–binding epidermal growth factor–like growth factor, transforming growth factor–β1, interferon–α and interferon–γ on the DNA synthesis of hepatocytes from cirrhotic and normal rats in primary culture. Cirrhosis was induced in male Sprague–Dawley rats by means of oral administration of 0.05% thioacetamide in drinking water for 4 mo. Hepatocytes were isolated by means of an in situ perfusion method, and DNA synthesis was assessed from the amount of DNA–incorporated [H]thymidine. Stimulation of the DNA synthesis of hepatocytes by hepatocyte growth factor, epidermal growth factor and heparin–binding epidermal growth factor–like growth factor was not different between normal and cirrhotic rat liver. Transforming growth factor–β1 inhibited the DNA synthesis of hepatocytes in both. However, the concentration of transforming growth factor–β1 giving a 50% inhibition of DNA synthesis was about two times higher in cirrhotic hepatocytes (0.11 ng/ml) than in normal hepatocytes (0.06 ng/ml). In cirrhotic hepatocytes, the expression of transforming growth factor–β type II receptor gene was about 50% of that in normal hepatocytes. The percent inhibitions of DNA synthesis by 1.25 × 104 U/ml of interferon–α were 51.6% ± 3.2% and 14.1% ± 7.7% in normal and cirrhotic hepatocytes, respectively, by 1.25 × 103 U/ml of interferon–γ 44.8% ± 10.3% and 19.9% ± 3.4%, respectively. These results suggest that inhibitory regulation of cell growth may be impaired in the hepatocytes from cirrhotic liver. (Hepatology 1994;20:1303–1308).
Limited usage of T-Cell receptor β chains and sequences of the complementarity determining region 3 of lymphocytes infiltrating in the liver of autoimmune hepatitis
Authors: Yuji Hoshino, Nobuyuki Enomoto, Namiki Izumi, Masayuki Kurosaki, Fumiaki Marumo, Chifumi Sato
Journal: Hepatology (1995)

To study the role of antigen-specific T lymphocytes in the pathogenesis of autoimmune hepatitis, messenger RNA of T-cell receptors (TCR) was analyzed in liver biopsy specimens from four patients with autoimmune hepatitis. Using the TCR β-chain variable region family specific oligonucleotides, a remarkable bias for the usage of β-chain variable region 3 was detected in all four patients. Therefore, nucleotide and amino acid sequences of the complementarity-determining region 3 rearranged to the β-chain variable region 3, which is a putative contact site for peptide fragments from antigens bound in the groove of the human leukocyte antigen molecule, was further analyzed in randomly selected 10 clones from each patient. An Asp-Arg-Pro motif in the complementarity-determining region 3 was identified in three of four patients with human leukocyte antigen DR4, and this motif was always rearranged to the β-chain junctional region 1.2. From these results, β-chain variable region 3 + , Asp-Arg-Pro + β-chain junctional region 1.2 + T-cell clones may be among the responsible lymphocytes involved in the liver damage in autoimmune hepatitis, especially in patients with human leukocyte antigen DR4. Thus, an analysis of the complementarity-determining region 3 may give us an important clue to clarify characteristics of target antigens included in autoimmune hepatitis. (Hepatology 1995; 22:142-147.)
Smoking Initiation by Adolescent Girls, 1944 Through 1988
Authors: John P. Pierce
Journal: JAMA (1994)

<h3>Objective.</h3> —To identify trends in smoking initiation among persons aged 10 to 20 years that might reflect the impact of specific targeting of tobacco advertising to women. <h3>Design.</h3> —Data from the National Health Interview Surveys on age of initiation of smoking (survey years 1970, 1978, 1979, 1980, 1987, and 1988) were used to construct age-specific rates of smoking initiation for males and females aged 10 to 20 years from 1944 through the middle 1980s. The raw rates were smoothed to allow trends to be more easily identified. <h3>Participants.</h3> —Information from 102 626 respondents was used. <h3>Results.</h3> —In 18- to 20-year-old women, initiation rates peaked in the early 1960s and steadily declined thereafter. In girls younger than 18 years, smoking initiation increased abruptly around 1967, when tobacco advertising aimed at selling specific brands to women was introduced. This increase was particularly marked in those females who never attended college (1.7-fold higher). Initiation rates for females younger than 18 years peaked around 1973, at about the same time sales of these brands peaked. After a steep postwar (1944 to 1949) decline, initiation rates in 18-to 20-year-old men did not decrease until the middle to late 1960s. Initiation rates for boys younger than 16 years showed little change during the entire study period. <h3>Conclusions.</h3> —The tobacco advertising campaigns targeting women, which were launched in 1967, were associated with a major increase in smoking uptake that was specific to females younger than the legal age for purchasing cigarettes. (<i>JAMA</i>. 1994;271:608-611)
Predisposition Genetic Testing for Late-Onset Disorders in Adults
Authors: Wendy C. McKinnon
Journal: JAMA (1997)

RAPID ADVANCES, such as those related to the Human Genome Project, have dramatically increased the number of available molecular genetic tests, and this number will only increase with future genetics research. Until recently, most such tests have been for rare monogenic conditions. Many of these single-gene disorders show signs or symptoms during childhood, while some, such as Huntington disease and adultonset polycystic kidney disease, have later onset. Molecular genetic tests have now become available for more common, complex conditions with onset later in life. Identification of cancer susceptibility genes<sup>1-6</sup>and of genes leading to several neurogenetic disorders, including Alzheimer disease<sup>7</sup>and some forms of ataxia,<sup>8</sup>represents the start of a cascade of genes to be identified that confer susceptibility to adult-onset diseases. Understanding of the genetic basis for other complex diseases, such as diabetes, heart disease, and psychiatric disorders, is advancing at a rapid pace.<sup>9-11</sup>These
Black-White Differences in Stroke Incidence in a National Sample
Authors: Steven J. Kittner
Journal: JAMA (1990)

Although national data have consistently shown an increased risk of death from stroke among blacks, few studies have addressed the reasons for this excess mortality. We compared the incidence of stroke among 1298 blacks and 7814 whites, aged 35 to 74 years, in the 10-year follow-up of the respondents from the First National Health and Nutrition Survey. Blacks had a higher estimated incidence of stroke than whites even after adjustment for age, hypertension, and diabetes mellitus; the relative risk was 1.4 (95% confidence interval, 1.0 to 2.0) for black women and 1.1 (95% confidence interval, 0.8 to 1.6) for black men. The relative risks for stroke associated with hypertension and diabetes mellitus were unrelated to race. Although efforts to treat hypertension and diabetes are among the most important public health measures for reducing stroke, a more complete understanding of the determinants of stroke may be required to account for the excess stroke risk experienced by blacks. (<i>JAMA</i>. 1990;264:1267-1270).
A Biomonitoring Study of Lead, Cadmium, and Mercury in the Blood of New York City Adults
Authors: Wendy McKelvey, R. Charon Gwynn, Nancy Jeffery, Daniel Kass, Lorna E. Thorpe, Renu K. Garg, Christopher D. Palmer, Patrick J. Parsons
Journal: Environmental Health Perspectives (2007)

ObjectivesWe assessed the extent of exposure to lead, cadmium, and mercury in the New York City (NYC) adult population.MethodsWe measured blood metal concentrations in a representative sample of 1,811 NYC residents as part of the NYC Health and Nutrition Examination Survey, 2004.ResultsThe geometric mean blood mercury concentration was 2.73 μg/L [95% confidence interval (CI), 2.58–2.89]; blood lead concentration was 1.79 μg/dL (95% CI, 1.73–1.86); and blood cadmium concentration was 0.77 μg/L (95% CI, 0.75–0.80). Mercury levels were more than three times that of national levels. An estimated 24.8% (95% CI, 22.2–27.7%) of the NYC adult population had blood mercury concentration at or above the 5 μg/L New York State reportable level. Across racial/ethnic groups, the NYC Asian population, and the foreign-born Chinese in particular, had the highest concentrations of all three metals. Mercury levels were elevated 39% in the highest relative to the lowest income group (95% CI, 21–58%). Blood mercury concentrations in adults who reported consuming fish or shellfish 20 times or more in the last 30 days were 3.7 times the levels in those who reported no consumption (95% CI, 3.0–4.6); frequency of consumption explained some of the elevation in Asians and other subgroups.ConclusionsHigher than national blood mercury exposure in NYC adults indicates a need to educate New Yorkers about how to choose fish and seafood to maximize health benefits while minimizing potential risks from exposure to mercury. Local biomonitoring can provide valuable information about environmental exposures.
Adult Cancer Pain
Authors: Robert A. Swarm, Amy Pickar Abernethy, Doralina L. Anghelescu, Costantino Benedetti, Sorin Buga, Charles Cleeland, Oscar A. deLeon-Casasola, June G. Eilers, Betty Ferrell, Mark Green, Nora A. Janjan, Mihir M. Kamdar, Michael H. Levy, Maureen Lynch, Rachel M. McDowell, Natalie Moryl, Suzanne A. Nesbit, Judith A. Paice, Michael W. Rabow, Karen L. Syrjala, Susan G. Urba, Sharon M. Weinstein, Mary Dwyer, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2013)

Pain is a common symptom associated with cancer and its treatment. Pain management is an important aspect of oncologic care, and unrelieved pain significantly comprises overall quality of life. These NCCN Guidelines list the principles of management and acknowledge the range of complex decisions faced in the management oncologic pain. In addition to pain assessment techniques, these guidelines provide principles of use, dosing, management of adverse effects, and safe handling procedures of pharmacologic therapies and discuss a multidisciplinary approach for the management of cancer pain.
Physicians' Behavior and Their Interactions With Drug Companies
Authors: Mary-Margaret Chren
Journal: JAMA (1994)

<h3>Objective.</h3> —It is controversial whether physicians' interactions with drug companies affect their behavior. To test the null hypothesis, that such interactions are not associated with physician behavior, we studied one behavior: requesting that a drug be added to a hospital formulary. <h3>Design.</h3> —Nested case-control study. <h3>Setting.</h3> —University hospital. <h3>Participants.</h3> —Full-time attending physicians. Case physicians were all 40 physicians who requested a formulary addition from January 1989 through October 1990. Control physicians were 80 randomly selected physicians who had not made requests. <h3>Main Exposure Measure.</h3> —Physician interactions with drug companies, as determined by survey of physicians (response rate, 88% [105/120]). <h3>Results.</h3> —Physicians who had requested that drugs be added to the formulary interacted with drug companies more often than other physicians; for example, they were more likely to have accepted money from companies to attend or speak at educational symposia or to perform research (odds ratio [OR], 5.1; 95% confidence interval [CI], 2.0 to 13.2). Furthermore, physicians were more likely than other physicians to have requested that drugs manufactured by specific companies be added to the formulary if they had met with pharmaceutical representatives from those companies (OR, 13.2; 95% CI, 4.8 to 36.3) or had accepted money from those companies (OR, 19.2; 95% CI, 2.3 to 156.9). These associations were consistent in multivariable analyses controlling for potentially confounding factors. Moreover, physicians were more likely to have requested formulary additions made by the companies whose pharmaceutical representatives they had met (OR, 4.9; 95% CI, 3.2 to 7.4) or from whom they had accepted money (OR, 1.7; 95% CI, 1.0 to 2.7) than they were to have requested drugs made by other companies. <h3>Conclusion.</h3> —Requests by physicians that drugs be added to a hospital formulary were strongly and specifically associated with the physicians' interactions with the companies manufacturing the drugs. (<i>JAMA</i>. 1994;271:684-689)